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Molecular imaging and cancer gene therapy

Cancer Gene Therapy (2016)Cite this article

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Abstract

Gene therapy is known as one of the most advanced approaches for therapeutic prospects ranging from tackling genetic diseases to combating cancer. In this approach, different viral and nonviral vector systems such as retrovirus, lentivirus, plasmid and transposon have been designed and employed. These vector systems are designed to target different therapeutic genes in various tissues and cells such as tumor cells. Therefore, detection of the vectors containing therapeutic genes and monitoring of response to the treatment are the main issues that are commonly faced by researchers. Imaging techniques have been critical in guiding physicians in the more accurate and precise diagnosis and monitoring of cancer patients in different phases of malignancies. Imaging techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are non-invasive and powerful tools for monitoring of the distribution of transgene expression over time and assessing patients who have received therapeutic genes. Here, we discuss most recent advances in cancer gene therapy and molecular approaches as well as imaging techniques that are utilized to detect cancer gene therapeutics and to monitor the patients’ response to these therapies worldwide, particularly in Iranian Academic Medical Centers and Hospitals.

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References

  1. Wang J, Mi P, Lin G, Wáng YXJ, Liu G, Chen X . Imaging-guided delivery of RNAi for anticancer treatment. Adv Drug Deliv Rev 2016; 104: 44–60.

    Article  CAS  Google Scholar 

  2. Veisani Y, Delpisheh A . Survival rate of gastric cancer in Iran; a systematic review and meta-analysis. Gastroenterol Hepatol Bed Bench 2016; 9: 78.

    PubMed  PubMed Central  Google Scholar 

  3. Mirzaei H, Gholamin S, Shahidsales S, Sahebkar A, Jafaari MR, Mirzaei HR et al. MicroRNAs as potential diagnostic and prognostic biomarkers in melanoma. Eur J Cancer 2016; 53: 25–32.

    Article  CAS  Google Scholar 

  4. Faghihloo E, Araei Y, Mohammadi M, Mirzaei H, Mohammadi H, Mokhtari-Azad T. The effect of oxamflatin on the E-cadherin expression in gastric cancer cell line. Cancer Gene Therapy 2016; 23: 396–399..

    Article  CAS  Google Scholar 

  5. Mirzaei H, Sahebkar A, Yazdi F, Salehi H, Jafari M, Namdar A et al. Circulating microRNAs in hepatocellular carcinoma: potential diagnostic and prognostic biomarkers. Curr Pharm Des 2016 (e-pub ahead of print).

  6. Simonian M, Mosallayi M, Mirzaei H . Circulating miR-21 as novel biomarker in gastric cancer: diagnostic and prognostic biomarker. J Cancer Res Ther 2016.

  7. Salarini R, Sahebkar A, Mirzaei H, Jaafari M, Riahi M, Hadjati J et al. Epi-drugs and Epi-miRs: moving beyond current cancer therapies. Curr Cancer Drug Targets 2016; 16: 773–788.

    Article  Google Scholar 

  8. Mirzaei HR, Sahebkar A, Salehi R, Nahand JS, Karimi E, Jaafari MR et al Boron neutron capture therapy: moving toward targeted cancer therapy. 2016.

    Article  CAS  Google Scholar 

  9. Mirzaei H, Sahebkar A, Jaafari M, Hadjati J, Javanmard S, Mirzaei H et al. PiggyBac as a novel vector in cancer gene therapy: current perspective. Cancer Gene Ther 2016; 23: 45–47.

    Article  CAS  Google Scholar 

  10. Shah K, Jacobs A, Breakefield X, Weissleder R . Molecular imaging of gene therapy for cancer. Gene Ther 2004; 11: 1175–1187.

    Article  CAS  Google Scholar 

  11. Sato T, Liu X, Nelson A, Nakanishi M, Kanaji N, Wang X et al. Reduced miR-146a increases prostaglandin E2 in chronic obstructive pulmonary disease fibroblasts. Am J Respir Crit Care Med 2010; 182: 1020–1029.

    Article  CAS  Google Scholar 

  12. Räty JK, Liimatainen T, Kaikkonen MU, Gröhn O, Airenne KJ, Ylä-Herttuala S . Non-invasive imaging in gene therapy. Mol Ther 2007; 15: 1579–1586.

    Article  Google Scholar 

  13. Rahou BH, El Rhazi K, Ouasmani F, Nejjari C, Bekkali R, Montazeri A et al. Quality of life in Arab women with breast cancer: a review of the literature. Health Quality Life Outcomes 2016; 14: 1.

    Article  Google Scholar 

  14. Borna H, Imani S, Iman M, Azimzadeh Jamalkandi S . Therapeutic face of RNAi: in vivo challenges. Exp Opin Biol Ther 2015; 15: 269–285.

    Article  CAS  Google Scholar 

  15. Naumova AV, Modo M, Moore A, Murry CE, Frank JA . Clinical imaging in regenerative medicine. Nat Biotechnol 2014; 32: 804–818.

    Article  CAS  Google Scholar 

  16. Jacobs A, Voges J, Reszka R, Lercher M, Gossmann A, Kracht L et al. Positron-emission tomography of vector-mediated gene expression in gene therapy for gliomas. Lancet 2001; 358: 727–729.

    Article  CAS  Google Scholar 

  17. la Fougère C, Suchorska B, Bartenstein P, Kreth F-W, Tonn J-C . Molecular imaging of gliomas with PET: opportunities and limitations. Neuro-oncology 2011; 13: 806–819.

    Article  Google Scholar 

  18. Jacobs A, Bräunlich I, Graf R, Lercher M, Sakaki T, Voges J et al. Quantitative kinetics of [124I] FIAU in cat and man. J Nucl Med 2001; 42: 467–475.

    CAS  PubMed  Google Scholar 

  19. Xu H, Guo R, Jin Y, Li B . [Gene-targeted radiation therapy mediated by radiation-sensitive promoter in lung adenocarcinoma and the feasibility of micro-PET/CT in evaluation of therapeutic effectiveness in small animals]. Zhongua Zhong Liu Za Zhi 2014; 36: 329–334.

    Google Scholar 

  20. Collins S, Hiraoka K, Inagaki A, Kasahara N, Tangney M, PET . imaging for gene & cell therapy. Curr Gene Ther 2012; 12: 20–32.

    Article  CAS  Google Scholar 

  21. Zinn K, Chaudhuri T, Buchsbaum D, Mountz J, Rogers B . Detection and measurement of in vitro gene transfer by gamma camera imaging. Gene Ther 2001; 8: 4.

    Article  Google Scholar 

  22. Buchsbaum DJ, Chaudhuri TR, Yamamoto M, Zemn KR . Gene expression imaging with radiolabeled peptides. Ann Nucl Med 2004; 18: 275–283.

    Article  CAS  Google Scholar 

  23. Bateman TM . Advantages and disadvantages of PET and SPECT in a busy clinical practice. J Nucl Cardiol 2012; 19: 3–11.

    Article  Google Scholar 

  24. Simonova M, Wall A, Weissleder R, Bogdanov A . Tyrosinase mutants are capable of prodrug activation in transfected nonmelanotic cells. Cancer Res 2000; 60: 6656–6662.

    CAS  PubMed  Google Scholar 

  25. Moore A, Josephson L, Bhorade RM, Basilion JP, Weissleder R . Human transferrin receptor gene as a marker gene for MR imaging 1. Radiology 2001; 221: 244–250.

    Article  CAS  Google Scholar 

  26. Xie L, Tan Y, Wang Z, Liu H, Zhang N, Zou C et al. Epsilon-caprolactone modified polyethyleneimine as efficient nanocarriers for siRNA delivery in vivo. ACS Appl Mater Interfaces 2016 (e-pub ahead of print).

  27. Aigner A . Gene silencing through RNA interference (RNAi) in vivo strategies based on the direct application of siRNAs. J Biotechnol 2006; 124: 12–25.

    Article  CAS  Google Scholar 

  28. Zhou B, Xiong Z, Zhu J, Shen M, Tang G, Peng C et al. PEGylated polyethylenimine-entrapped gold nanoparticles loaded with gadolinium for dual-mode CT/MR imaging applications. Nanomedicine 2016; 11: 1639–1652.

    Article  CAS  Google Scholar 

  29. Ichikawa T, Högemann D, Saeki Y, Tyminski E, Terada K, Weissleder R et al. MRI of transgene expression: correlation to therapeutic gene expression. Neoplasia 2002; 4: 523–530.

    Article  CAS  Google Scholar 

  30. Kircher MF, Allport JR, Graves EE, Love V, Josephson L, Lichtman AH et al. In vivo high resolution three-dimensional imaging of antigen-specific cytotoxic T-lymphocyte trafficking to tumors. Cancer Res 2003; 63: 6838–6846.

    CAS  PubMed  Google Scholar 

  31. Tavri S, Jha P, Meier R, Henning TD, Müller T, Hostetter D et al. Optical imaging of cellular immunotherapy against prostate cancer. Mol Imaging 2009; 8: 1.

    Article  Google Scholar 

  32. Guimaraes MD, Hochhegger B, Santos MK, Santana PRP, Sousa Júnior AS, Souza LS et al. Magnetic resonance imaging of the chest in the evaluation of cancer patients: state of the art. Radiol Bras 2015; 48: 33–42.

    Article  Google Scholar 

  33. Li Z, Qiao H, Lebherz C, Choi SR, Zhou X, Gao G et al. Creatine kinase, a magnetic resonance-detectable marker gene for quantification of liver-directed gene transfer. Hum Gene Ther 2005; 16: 1429–1438.

    Article  CAS  Google Scholar 

  34. Matsumoto S . Prediction of cancer treatment response by physiologic and metabolic imaging. Yakugaku Zasshi 2016; 136: 1101.

    Article  CAS  Google Scholar 

  35. Albers MJ, Bok R, Chen AP, Cunningham CH, Zierhut ML, Zhang VY et al. Hyperpolarized 13C lactate, pyruvate, and alanine: noninvasive biomarkers for prostate cancer detection and grading. Cancer Res 2008; 68: 8607–8615.

    Article  CAS  Google Scholar 

  36. Nelson SJ, Kurhanewicz J, Vigneron DB, Larson PE, Harzstark AL, Ferrone M et al. Metabolic imaging of patients with prostate cancer using hyperpolarized [1-13C] pyruvate. Sci Transl Med 2013; 5: 198ra08–ra08.

    Article  Google Scholar 

  37. Cicchelero L, Denies S, Haers H, Vanderperren K, Stock E, Van Brantegem L et al. Intratumoural interleukin 12 gene therapy stimulates the immune system and decreases angiogenesis in dogs with spontaneous cancer. Vet Comp Oncol 2016.

  38. Aalinkeel R, Nair B, Chen CK, Mahajan SD, Reynolds JL, Zhang H et al. Nanotherapy silencing the interleukin‐8 gene produces regression of prostate cancer by inhibition of angiogenesis. Immunology 2016; 148: 387–406.

    Article  CAS  Google Scholar 

  39. Bournet B, Buscail C, Muscari F, Cordelier P, Buscail L . Targeting KRAS for diagnosis, prognosis, and treatment of pancreatic cancer: Hopes and realities. Eur J Cancer 2016; 54: 75–83.

    Article  CAS  Google Scholar 

  40. Brindle K . New approaches for imaging tumour responses to treatment. Nat Rev Cancer 2008; 8: 94–107.

    Article  CAS  Google Scholar 

  41. Bogdanov A, Weissleder R . The development of in vivo imaging systems to study gene expression. Trends Biotechnol 1998; 16: 5–10.

    Article  CAS  Google Scholar 

  42. Massoud TF, Gambhir SS . Molecular imaging in living subjects: seeing fundamental biological processes in a new light. Genes Dev 2003; 17: 545–580.

    Article  CAS  Google Scholar 

  43. Nedaeinia R, Sharifi M, Avan A, Kazemi M, Rafiee L, Ghayour-Mobarhan M et al. Locked nucleic acid anti-miR-21 inhibits cell growth and invasive behaviors of a colorectal adenocarcinoma cell line: LNA-anti-miR as a novel approach. Cancer Gene Ther 2016; 23: 246–253.

    Article  CAS  Google Scholar 

  44. Campadelli P, Casiraghi E, Artioli D . A fully automated method for lung nodule detection from postero-anterior chest radiographs. IEEE Trans Med Imaging 2006; 25: 1588–1603.

    Article  Google Scholar 

  45. Simon CJ, Dupuy DE (eds) Seminars in Musculoskeletal Radiology. Thieme Medical Publishers Inc.: New York, NY, USA, 2006.

    Google Scholar 

  46. Bhattacharyya M, Ryan D, Carpenter R, Vinnicombe S, Gallagher C . Using MRI to plan breast-conserving surgery following neoadjuvant chemotherapy for early breast cancer. Br J Cancer 2008; 98: 289–293.

    Article  CAS  Google Scholar 

  47. Liapi E, Geschwind J-F, Vossen JA, Buijs M, Georgiades CS, Bluemke DA et al. Functional MRI evaluation of tumor response in patients with neuroendocrine hepatic metastasis treated with transcatheter arterial chemoembolization. Am J Roentgenol 2008; 190: 67–73.

    Article  Google Scholar 

  48. Plewes DB, Bishop J, Samani A, Sciarretta J . Visualization and quantification of breast cancer biomechanical properties with magnetic resonance elastography. Phys Med Biol 2000; 45: 1591.

    Article  CAS  Google Scholar 

  49. Helbich TH, Roberts TP, Gossmann A, Wendland MF, Shames DM, Adachi M et al. Quantitative gadopentetate‐enhanced MRI of breast tumors: testing of different analytic methods. Magn Reson Med 2000; 44: 915–924.

    Article  CAS  Google Scholar 

  50. Bartella L, Huang W . Proton (1H) MR spectroscopy of the breast 1. Radiographics 2007; 27: S241–S252.

    Article  Google Scholar 

  51. Kopelman D, Inbar Y, Hanannel A, Dank G, Freundlich D, Perel A et al. Magnetic resonance‐guided focused ultrasound surgery (MRgFUS). Four ablation treatments of a single canine hepatocellular adenoma. HPB 2006; 8: 292–298.

    Article  Google Scholar 

  52. Vogl TJ, Mayer HP, Zangos S, Selby JB Jr, Ackermann H, Mayer FB . Prostate Cancer: MR imaging–guided galvanotherapy—technical development and first clinical results 1. Radiology 2007; 245: 895–902.

    Article  Google Scholar 

  53. Narayan P, Gajendran V, Taylor SP, Tewari A, Presti JC, Leidich R et al. The role of transrectal ultrasound-guided biopsy-based staging, preoperative serum prostate-specific antigen, and biopsy Gleason score in prediction of final pathologic diagnosis in prostate cancer. Urology 1995; 46: 205–212.

    Article  CAS  Google Scholar 

  54. Fahey B, Nelson R, Bradway D, Hsu S, Dumont D, Trahey G . In vivo visualization of abdominal malignancies with acoustic radiation force elastography. Phys Med Biol 2007; 53: 279.

    Article  Google Scholar 

  55. Paliwal S, Sundaram J, Mitragotri S . Induction of cancer-specific cytotoxicity towards human prostate and skin cells using quercetin and ultrasound. Br J Cancer 2005; 92: 499–502.

    Article  CAS  Google Scholar 

  56. Pogue BW, Poplack SP, McBride TO, Wells WA, Osterman KS, Osterberg UL et al. Quantitative hemoglobin tomography with diffuse near-infrared spectroscopy: pilot results in the breast 1. Radiology 2001; 218: 261–266.

    Article  CAS  Google Scholar 

  57. Kao T-J, Saulnier GJ, Xia H, Tamma C, Newell J, Isaacson D . A compensated radiolucent electrode array for combined EIT and mammography. Physiol Meas 2007; 28: S291.

    Article  Google Scholar 

  58. Ntziachristos V, Yodh A, Schnall MD, Chance B . MRI-guided diffuse optical spectroscopy of malignant and benign breast lesions. Neoplasia 2002; 4: 347–354.

    Article  Google Scholar 

  59. Hung S-C, Deng W-P, Yang WK, Liu R-S, Lee C-C, Su T-C et al. Mesenchymal stem cell targeting of microscopic tumors and tumor stroma development monitored by noninvasive in vivo positron emission tomography imaging. Clin Cancer Res 2005; 11: 7749–7756.

    Article  CAS  Google Scholar 

  60. Cascini GL, Avallone A, Delrio P, Guida C, Tatangelo F, Marone P et al. 18 F-FDG PET is an early predictor of pathologic tumor response to preoperative radiochemotherapy in locally advanced rectal cancer. J Nucl Med 2006; 47: 1241–1248.

    CAS  PubMed  Google Scholar 

  61. Ranji P, Kesejini TS, Saeedikhoo S, Alizadeh AM . Targeting cancer stem cell-specific markers and/or associated signaling pathways for overcoming cancer drug resistance. Tumor Biol 2016 (e-pub ahead of print).

  62. Hendijani F, Javanmard SH . Dual protective and cytotoxic benefits of mesenchymal stem cell therapy in combination with chemotherapy/radiotherapy for cancer patients. Crit Rev Eukaryot Gene Expr 2015; 25: 203–207.

    Article  Google Scholar 

  63. Bolhassani A, Javanzad S, Saleh T, Hashemi M, Aghasadeghi MR, Sadat SM . Polymeric nanoparticles: potent vectors for vaccine delivery targeting cancer and infectious diseases. Hum Vaccin Immunother 2014; 10: 321–332.

    Article  CAS  Google Scholar 

  64. Imani R, Shao W, Taherkhani S, Emami SH, Prakash S, Faghihi S . Dual-functionalized graphene oxide for enhanced siRNA delivery to breast cancer cells. Colloids Surf B Biointerfaces 2016; 147: 315–325.

    Article  CAS  Google Scholar 

  65. Maleklou N, Allameh A, Kazemi B . Targeted delivery of vitamin D3-loaded nanoparticles to C6 glioma cell line increased resistance to doxorubicin, epirubicin, and docetaxel in vitro. In Vitro Cell Dev Biol Anim 2016 (e-pub ahead of print).

  66. Aslani S, Jafari N, Javan MR, Karami J, Ahmadi M, Jafarnejad M . Epigenetic modifications and therapy in multiple sclerosis. Neuromol Med 2016 (e-pub ahead of print).

  67. Davudian S, Mansoori B, Shajari N, Mohammadi A, Baradaran B . BACH1, the master regulator gene: a novel candidate target for cancer therapy. Gene 2016; 588: 30–37.

    Article  CAS  Google Scholar 

  68. Majidinia M, Yousefi B . Long non-coding RNAs in cancer drug resistance development. DNA Rep 2016; 45: 25–33.

    Article  CAS  Google Scholar 

  69. Malih S, Saidijam M, Malih N . A brief review on long noncoding RNAs: a new paradigm in breast cancer pathogenesis, diagnosis and therapy. Tumor Biol 2016; 37: 1479–1485.

    Article  CAS  Google Scholar 

  70. Mirzaei HR, Mirzaei H, Lee SY, Hadjati J, Till BG. Prospects for chimeric antigen receptor (CAR) T cells: a potential game changer for adoptive T cell cancer immunotherapy. Cancer Lett 2016; 380: 413–423..

    Article  CAS  Google Scholar 

  71. Mirzaei H, Avan A, Salehi H, Sahebkar A, Namdar A, Mirzaei HR et al. Deciphering biological characteristics of tumorigenic subpopulations in human colorectal cancer reveals cellular plasticity. J Res Med Sci 2016; 21..

    Article  Google Scholar 

  72. Mohammadi M, Goodarzi M, Jaafari M, Mirzaei H, Mirzaei H. Circulating microRNA: a new candidate for diagnostic biomarker in neuroblastoma. Cancer Gene Ther 2016; 23: 371–372..

    Article  CAS  Google Scholar 

  73. Fathullahzadeh S, Mirzaei H, Honardoost M, Sahebkar A, Salehi M. Circulating microRNA-192 as a diagnostic biomarker in human chronic lymphocytic leukemia. Cancer Gene Ther 2016; 23: 327–332..

    Article  CAS  Google Scholar 

  74. Mohammadi M, Jaafari M, Mirzaei H, Mirzaei H. Mesenchymal stem cell: a new horizon in cancer gene therapy. Cancer Gene Ther 2016; 23: 285–286..

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Bozorgmehr Imaging Center, Isfahan University of Medical Sciences, Isfahan, Iran

    Z Saadatpour

  2. Council for Nutritional and Environmental Medicine, Mo i Rana, Norway

    G Bjorklund

  3. Department of Neurological and Movement Sciences, University of Verona, Verona, Italy

    S Chirumbolo

  4. Department of Oral and Maxillofacial Radiology, School of Dentistry, Mazandaran University of Medical Sciences, Sari, Iran

    M Alimohammadi

  5. Department of Periodontology, School of Dentistry, Mazandaran University of Medical Sciences, Sari, Iran

    H Ehsani

  6. Department of Oral and Maxillofacial Radiology, School of Dentistry, Kerman University of Medical Sciences, Kerman, Iran

    H Ebrahiminejad

  7. Department of Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    H Pourghadamyari

  8. Department of Endodontics, School of Dentistry, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

    B Baghaei

  9. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    H R Mirzaei

  10. Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    A Sahebkar

  11. Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    H Mirzaei

  12. Department of Oral and Maxillofacial Radiology, School of Dentistry, Lorestan University of Medical Sciences, Khorramabad, Iran

    M Keshavarzi

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Correspondence to M Keshavarzi.

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Saadatpour, Z., Bjorklund, G., Chirumbolo, S. et al. Molecular imaging and cancer gene therapy. Cancer Gene Ther (2016). https://doi.org/10.1038/cgt.2016.62

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